The medial prefrontal cortex: coordinator of autonomic, neuroendocrine and behavioural responses to stress

Abstract

Responding to real or potential threats in the environment requires the coordination of autonomic, neuroendocrine and behavioural processes to promote adaptation and survival. These diverging systems necessitate input from the limbic forebrain to integrate and modulate functional output in accordance with contextual demand. In the present review, we discuss the potential role of the medial prefrontal cortex (mPFC) as a coordinator of behavioural and physiological stress responses across multiple temporal and contextual domains. Furthermore, we highlight converging evidence from rodent and human research indicating the necessity of the mPFC for modulating physiological energetic systems to mobilise or limit energetic resources as needed to ultimately promote behavioural adaptation in the face of stress. We review the literature indicating that glucocorticoids act as one of the primary messengers in the reallocation of energetic resources having profound effects locally within the mPFC, as well as shaping how the mPFC acts within a network of brain structures to modulate responses to stress. Finally, we discuss how both rodent and human studies point toward a critical role of the mPFC in the coordination of anticipatory responses to stress and why this distinction is an important one to make in stress neurobiology.

Keywords: autonomic nervous system; executive function; glucocorticoids; hypothalamic-pituitary-adrenocortical axis; prefrontal cortex; stress.

Figure 1

mPFC Neuroanatomy. Sagittal (left) and coronal (right) sections of the medial prefrontal cortex (mPFC) showing the anterior cingulate (AC), prelimbic (PL), and infralimbic (IL) cortices. The dotted line on the sagittal view indicates the location of the coronal section. Other abbreviations as follows: olfactory bulb (OB), forceps minor of the corpus callosum (FMI), corpus callosum (CC), dorsal AC (dAC), ventral AC (vAC), optic chiasm (OX).

Figure 2

Intrinsic Circuitry and Efferents of the mPFC. The mPFC is under tight regulatory control of local interneuron populations that limit the predominantly glutamatergic output of the mPFC. Somatostatin (SS) and parvalbumin (PV) are two of the primary interneuron subtypes within the mPFC that provide dendritic and perisomatic inhibition, respectively. The mPFC projects to numerous subcortical and hindbrain targets, e.g. the bed nucleus of the stria terminalis (BST), hypothalamic subnuclei, and brainstem that mediate its effects on neuroendocrine and autonomic responses to stress. Other abbreviations as follows: corticotropin-releasing hormone (CRH) and acetylcholine (ACh).

Figure 3

Prefrontal Coordination of Energetic Systems. A schematic representation of the potential role that the medial prefrontal cortex could play in coordinating activity between the autonomic and hypothalamic-pituitary-adrenocortical (HPA) axis to regulate both emotional/reactive and executive functions in response to environmental stimuli.